This is a competitive renewal for the Medical Scientist Training Program (MSTP) at Mount Sinai School of Medicine (MSSM). We are asking for an increase in the number of trainees supported by the NIH to 24 (from 19). During the last 5 yrs, MSSM has undergone a major expansion of its research enterprise, including the recruitment of 45 new Graduate School Faculty, representing a wide array of research disciplines, the launching of a number of institution-wide state-of-the-art core facilities for technical support and education, and a 35% increase in NIH funding. MSSM is moving forward with a new Strategic Plan, the centerpiece of which is the construction of a Translational Research building by 2010 and broad new recruitment initiatives in basic and clinical research. This institutional research growth is paired with a significant and rapid increase in the number of qualified MSTP applicants during the current grant period as compared to the previous one. The institution is fully committed to supporting the growth of the number of physician-scientists and MSTP trainees. Thus, we feel that the requested increase in the number of trainees is well justified. Graduate training continues to be organized in 6 Multidisciplinary Training Areas (MTAs). Ongoing changes in the Graduate School curriculum continue to provide new flexibility and maximize opportunities for trainees to apply their basic science training to medicine. The new curriculum introduced into the Medical School in 2000, aiming to strike an optimal balance of lecture versus small group learning with a focus on problem-based learning, has been a resounding success;it allows MSTP students to complete many of their Graduate School course requirements in the first year and provides new opportunities to interact with academically-oriented clinicians. The MSTP has a new Director, Dr. Diomedes Logothetis, who together with the leadership of the program, particularly Associate Director Lisa Satlin, have managed a seamless transition in leadership and have stimulated the significant growth in the number of applicants. Most trainees matriculate into the program from the extramural applicant pool but additional outstanding applicants are considered from intramural MD and PhD (PhD-to-MD/PhD track) programs. All trainees participate in Core PhD coursework and Research Rotations during the first year of the program. Advisory oversight helps trainees choose a preceptor and guide, monitor, and integrate all aspects of their progress to the completion of their PhD thesis. All trainees complete their PhD work before entering the clinical clerkships. A new course entitled "Clinical Investigation for the Translational Scientist" aims to inform second year students about human subjects related research. An intensive clinical refresher, and a flexible schedule help trainees integrate easily into the clinical setting. New programs are designed to provide comprehensive career guidance to help ensure that graduates can achieve their long-term clinical and independent research goals.